Tonix Files for Patent for TNX-1500 to Treat Autoimmune Diseases

Tonix Pharmaceuticals has filed a patent application with the World Intellectual Property Organization covering the use of TNX-1500 — its third-generation anti-CD154 antibody — for the prevention and treatment of autoimmune diseases, such as multiple sclerosis (MS), and organ transplant rejection.

“There remains a significant need for new treatments with improved activity and tolerability to prevent or treat organ transplant rejection and to treat autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis,” Seth Lederman, MD, Tonix’s president and CEO, said in a press release.

The application, number WO/2021/001458 and titled “Anti-CD154 Antibodies and Uses Thereof,” intends coverage of all anti-CD154 antibodies (including TNX-1500) engineered to decrease binding to Fc-gammaRII (FcγRII) — a membrane receptor whose activation increases the risk of thrombosis — and compounds comprising such antibodies.

Of note, thrombosis is the formation of a blood clot inside a blood vessel, obstructing blood flow.

The intended patent also covers any use of such molecules to suppress immune responses, including those involved in transplant rejection, and autoimmune and inflammatory diseases.

If the claims are granted, the patent could potentially provide U.S. coverage through 2040. That does not include any possible patent term extensions or adjustments.

CD154, also known as CD40 ligand (CD40L), is a member of the tumor necrosis factor (TNF) superfamily of receptor molecules that are involved in chronic inflammation. It is mainly present on the surface of activated T helper cells, a type of cell that mediates immune responses. In these cells, CD154 is involved in their immune function and the activation of other immune cells.

Given that T helper cells are known to be involved in the abnormal immune responses that characterize autoimmune disorders, such as MS, and in the responses that drive organ transplant rejection, approaches designed to block CD154 are thought to have great therapeutic potential in such areas.

Antibodies designed to bind to and block the activity of CD154 are one such promising approach.

“Nearly 30 years ago my laboratory at Columbia University generated the first anti-CD40-ligand [antibody], discovered and characterized human CD40-ligand and elucidated the molecular basis of T cell helper function,” Lederman said.

“Our studies and those of others generated a substantial body of evidence in humans and animals that indicates anti-CD40-ligand [antibodies] have the potential to be an important therapeutic option for preventing or treating transplant organ rejection and for treating autoimmune disorders,” he added.

However, the first generation of such antibodies were limited, Lederman noted, due to the interaction with “a cell surface receptor called FcγRII, which resulted in an increased risk of thrombosis.”

While second-generation anti-CD154 antibodies were designed to “dramatically” reduce their binding to this receptor, they “had other issues, including decreased efficacy,” Lederman said.

“TNX-1500 is a third generation [anti-CD154 antibody] that has been designed by protein engineering to decrease FcγRII binding and the potential for thrombosis, while retaining efficacy,” he said. “We believe TNX-1500 has the potential for treating and preventing organ transplant rejection and treating autoimmunity.”

Lederman also noted that the company expects good manufacturing practice (GMP) production of TNX-1500 to be ready in the third quarter of 2021. Required before a potential medicine can be tested in humans, GMP refers to a quality control system meant to ensure that all batches of a product consistently adhere to a certain standard.